Method and devices for preventing restenosis in cardiovascular stents

Abstract

Described herein are devices and methods fabricating devices having nanostructures that allow adhesion or growth of one cell type, such as endothelial cells, more than another cell type, such as smooth muscle cells. In particular, stent covers having such nanostructures are described, and methods for fabricating these stent covers. Also described herein are methods for optimizing the nanostructures forming the devices.

1. A method of forming a stent cover having a nanostructure, the method comprising:
 forming a protective patterned layer on an outer surface of a sacrificial mandrel; 
 layering a plurality of nanostructural material layers at least partially over the protective patterned layer, wherein each nanostructural material is layered over the adjacent nanostructural material; 
 depositing a shape memory alloy at least partially over the plurality of nanostructural material layers; 
 crystallizing the shape memory alloy; 
 removing the sacrificial mandrel; and 
 etching through the plurality of nanostructural material layers to form a plurality of wells, wherein the walls of each well are striated layers of the plurality of nanostructural materials, and the well are at least surrounded by the shape memory alloy. 
 
     
     
       2. The method of  claim 1 , wherein the shape memory alloy is a nickel-titanium alloy. 
     
     
       3. The method of  claim 1 , further comprising fenestrating the shape memory alloy. 
     
     
       4. The method of  claim 1 , wherein the sacrificial mandrel is formed of copper. 
     
     
       5. The method of  claim 1 , wherein the protective patterned layer is formed by photolithographically patterning a chromium layer on the sacrificial mandrel. 
     
     
       6. The method of  claim 1 , wherein first nanostructural material is selected from the group consisting of: Ti, TiNi, Au, Ni, Al, Fe, Pt, Hf. 
     
     
       7. The method of  claim 1 , wherein layering comprises depositing alternately first and second nanostructural materials at least partially over the protective patterned layer. 
     
     
       8. The method of  claim 7 , wherein the second nanostructural material is applied to a thickness of between about 10 nm and about 500 nm. 
     
     
       9. The method of  claim 1 , wherein the nanostructural materials are each applied to a thickness of between about 10 nm and about 500 nm. 
     
     
       10. The method of  claim 1  wherein the nanostructural materials comprise one or more pairs of sub-layers wherein each sub-layer is between about 10 nm and about 500 nm thick. 
     
     
       11. A method of controlling the growth of cells, the method comprising: patterning a substrate to have an organized nanostructure for cell growth by:
 a. layering a first nanostructural material at least partially over a substrate; 
 b. layering a second nanostructural material at least partially over the layer from step a; 
 c. repeating steps a and b to form a plurality of alternating layers of the first nanostructural material and the second nanostructural material; 
 d. forming a patterned layer on the outer surface of the plurality of alternating layers; and 
 e. etching the nonstructural material to form a nanostructured surface comprising walls striated by alternating layers of the first and second nanostructural materials; and
 placing cells on the patterned substrate. 
 
 
     
     
       12. The method of  claim 11 , wherein the step of layering the second nanostructural material comprises depositing a shape memory alloy at least partially over the first nanostructural material layer. 
     
     
       13. The method of  claim 12 , further comprising crystallizing the shape memory alloy. 
     
     
       14. A method of forming a stent cover having a nanostructure, the method comprising:
 forming a protective patterned layer on an outer surface of a sacrificial mandrel; 
 layering a plurality of nanostructural material layers at least partially over the protective patterned layer, wherein each nanostructural material is layered over the adjacent nanostructural material; 
 depositing a shape memory alloy at least partially over the plurality of nanostructural material layers; 
 crystallizing the shape memory alloy; 
 removing the sacrificial mandrel; and 
 etching through the plurality of nanostructural material layers to form a plurality of islets, wherein the walls of each islet are striated layers of the plurality of nanostructural materials, and the islets are at least partially surrounded by shape memory alloy.